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Autologous skeletal muscle derived cells expressing a novel functional dystrophin provide a potential therapy for Duchenne Muscular Dystrophy

Lookup NU author(s): Dr Mojgan Reza, Dr Steven Laval, Professor Hanns Lochmuller



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Autologous stem cells that have been genetically modified to express dystrophin are a possible means of treating Duchenne Muscular Dystrophy (DMD). To maximize the therapeutic effect, dystrophin construct needs to contain as many functional motifs as possible, within the packaging capacity of the viral vector. Existing dystrophin constructs used for transduction of muscle stem cells do not contain the nNOS binding site, an important functional motif within the dystrophin gene. In this proof-of-concept study, using stem cells derived from skeletal muscle of a DMD patient (mdcs) transplanted into an immunodeficient mouse model of DMD, we report that two novel dystrophin constructs, C1 (Delta R3-R13) and C2 (Delta H2-R23), can be lentivirally transduced into mdcs and produce dystrophin. These dystrophin proteins were functional in vivo, as members of the dystrophin glycoprotein complex were restored in muscle fibres containing donor-derived dystrophin. In muscle fibres derived from cells that had been transduced with construct C1, the largest dystrophin construct packaged into a lentiviral system, nNOS was restored. The combination of autologous stem cells and a lentivirus expressing a novel dystrophin construct which optimally restores proteins of the dystrophin glycoprotein complex may have therapeutic application for all DMD patients, regardless of their dystrophin mutation.

Publication metadata

Author(s): Meng JH, Counsell JR, Reza M, Laval SH, Danos O, Thrasher A, Lochmuller H, Muntoni F, Morgan JE

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2016

Volume: 6

Online publication date: 27/01/2016

Acceptance date: 17/12/2015

Date deposited: 05/04/2016

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/srep19750


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Funder referenceFunder name
GOSH Biomedical Research Centre
Great Ormond Street Hospital Children's Charity
National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust
UCL Institute of Child Health Flow Cytometry Core Facility and Biological Service Unit
MRC Centre for Neuromuscular Diseases Biobank
University College London
Wellcome Trust University Award
305121European Commission
305444European Commission